Study Hypothesis: We hypothesize that cellular markers from nasal epithelial cells and blood lymphocytes can serve as potential biomarkers reflect the underlying inflammatory state of the lung and will be helpful in determining the presence of a CF pulmonary exacerbation and its overall severity.

These subjects will undergo epithelial cells and blood lymphocyte extraction. Nasal curettage will be performed to obtain nasal epithelial cells and blood will be obtained to isolate circulating lymphocytes one time from these subjects (age 15 years and above) when they are in their usual state of well-health. These cells will be studied in vitro.

Procedure: epithelial cells and blood lymphocyte extraction

Nasal curettage will be performed from each nostril to obtain nasal epithelial cells. Venipuncture will be performed and up to 60-ml of blood will be obtained from which neutrophils will be isolated.

Exacerbating subjects with CF

These subjects will undergo epithelial cells and blood lymphocyte extraction. Nasal curettage will be performed to obtain nasal epithelial cells and blood will be obtained to isolate circulating lymphocytes one time from these subjects (age 15 years and above) at the beginning and end of treatment for a pulmonary exacerbation. These cells will be studied in vitro.

Procedure: epithelial cells and blood lymphocyte extraction

Nasal curettage will be performed from each nostril to obtain nasal epithelial cells. Venipuncture will be performed and up to 60-ml of blood will be obtained from which neutrophils will be isolated.

Stable subjects with asthma

These subjects will undergo epithelial cells and blood lymphocyte extraction. Nasal curettage will be performed to obtain nasal epithelial cells and blood will be obtained to isolate circulating lymphocytes one time from these subjects (age 15 years and above) when they are in their usual state of well-health. These cells will be studied in vitro. This is the disease control group.

Procedure: epithelial cells and blood lymphocyte extraction

Nasal curettage will be performed from each nostril to obtain nasal epithelial cells. Venipuncture will be performed and up to 60-ml of blood will be obtained from which neutrophils will be isolated.

Healthy volunteers

These subjects will undergo epithelial cells and blood lymphocyte extraction. Nasal curettage will be performed to obtain nasal epithelial cells and blood will be obtained to isolate circulating lymphocytes one time from these subjects (age 15 years and above) when they are in their usual state of well-health. These cells will be studied in vitro. This is the control group

Procedure: epithelial cells and blood lymphocyte extraction

Nasal curettage will be performed from each nostril to obtain nasal epithelial cells. Venipuncture will be performed and up to 60-ml of blood will be obtained from which neutrophils will be isolated.

Detailed Description:

Cystic fibrosis (CF) is the most common lethal genetic disease in the US afflicting approximately 30,000 people. Chronic disease of the respiratory tract, which is responsible for early death, affects both the upper and lower airways.

We propose to utilize cells (blood lymphocytes and nasal epithelial cells) that are readily accessible and are known to express the cystic fibrosis transmembrane conductance regulator (CFTR) and therefore candidates to express markers of the downstream consequences of CFTR deficiency.

A marker that indicates the inflammatory state of the lung would be useful to identify infective/inflammatory exacerbations as opposed to worsening due to pulmonary vascular disease or simply upper airway infection. This marker might help to guide therapy for intensity and duration. Evidence in mice suggest that lymphocytes may be a driving force for inflammation in the CF lung, particularly during exacerbations, and also that human CF lymphocytes have dysfunctional production of cytokines.

Specific Aims:

To identify markers in nasal epithelial cells or blood lymphocytes that distinguish CF patients from those with functional CFTR (healthy volunteers and patients with asthma). If successful this could become a marker for CFTR correction by drugs or other systemic therapies.

To identify markers in blood lymphocytes that will identify inflammatory status (ie, distinguish an active exacerbation from return to clinical stability) in CF patients. This could become a marker for infectious exacerbations of CF airway disease.

Eligibility

Ages Eligible for Study:

15 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Sampling Method:

Non-Probability Sample

Study Population

Nasal epithelial cells and blood will be obtained from four groups of subjects age 15 years and older: Stable subjects with CF at baseline, Subjects with CF at the beginning and end of treatment for a pulmonary exacerbation, stable subjects with asthma, and healthy voulnteers

Criteria

Stable CF Patients:

Inclusion Criteria:

Male or female >= 15 years of age

Confirmed diagnosis of CF

Clinically stable with no evidence of acute upper respiratory tract infection or current pulmonary exacerbation within the previous month

Ability to understand and sign a written informed consent and comply with the requirements of the study

Exclusion Criteria:

Chronic use of a medication with anti-neutrophil or anti-inflammatory effect (ibuprofen, systemic or inhaled corticosteroids, or other immunosuppressive agents, etc

Oxygen saturation <92% on room air

Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the subject or the quality of the data

CF patients with pulmonary exacerbations:

Male of female >= 15 years of age Confirmed diagnosis of CF

Patient meets a modified definition for a pulmonary exacerbation based upon Fuchs criteria which is treated with intravenous antibiotics for any 4 of the following 12 signs or symptoms:

Ability to understand and sign a written informed consent and comply with the requirements of the study

Exclusion criteria for CF patients with pulmonary exacerbation:

Concurrent use a medication with anti-neutrophil or anti-inflammatory effect within the previous 4 weeks

Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the subject or the quality of the data.

Inclusion Criteria - Asthma patients

Male or female >= 15 years of age

Physician diagnosed asthma

Clinically stable with no evidence of acute upper or lower respiratory tract infection or current pulmonary exacerbation within the previous month

Exclusion Criteria - Asthma patients

Chronic use of a medication with anti-neutrophil or anti-inflammatory effect within the previous 4 weeks

Treated for an asthma exacerbation with the previous 4 weeks

Treated with oral corticosteroids within the previous 4 weeks

Oxygen saturation <92% on room air

Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the subject or the quality of the data.

Inclusion Criteria for Healthy Volunteers

Male or female >= 18 years of age

Free of any chronic medical condition

Clinically stable with no evidence of acute upper or lower respiratory tract infection within the previous month

Ability to understand and sign a written informed consent and comply with the requirements of the study

Exclusion Criteria for Healthy Volunteers

Use of a medication with anti-neutrophil or anti-inflammatory effect within the previous 4 months

Presence of any chronic medical condition

Oxygen saturation <92% on room air

Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the subject or the quality of the data

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00381628